The development of tracheal cartilage degeneration and inflammation of the seromucinous glands of the oropharynx may be a factor causing early mortalities in long-term studies with Fischer-344 (F-344) rats. The presence of these lesions was investigated in groups of male and female F-344 rats killed at 6, 19, and 32 wk of age. Half of the rats killed at 19 and 32 wk of age were sham treated with water (pH 10) by daily oral gavage for a duration of 13 or 26 wk prior to autopsy in order to detect any influence on the laryngotracheal cavity due to dosing technique. A clear age-associated increase in severity and incidence of chondroid degeneration of the tracheal and laryngeal cartilage was revealed, with an onset as early as 6 wk of age. After 19 wk, a high frequency of oropharyngeal granuloma formation was found. No relationship of the lesions to the gavage technique was apparent. The F-344 rat strain may possess a predisposition for inflammatory and degenerative changes in the oropharyngeal and laryngotracheal cavity, changes that can lead to increased and unexpected mortality rates in nonclinical safety studies (7).